A novel ING2 isoform, ING2b, synergizes with ING2a to prevent cell cycle arrest and apoptosis.
We identified a novel inhibitor of growth family member 2 (ING2) isoform, ING2b, which shares exon 2 with ING2a, but lacks the N-terminal p53 binding region. Contrary to ING2a, ING2b's promoter has no p53 binding sites. Consistently, activation of p53 led to suppression of ING2a, leaving ING2b unaffected. Through isoform-specific targeting, we showed that ING2a knockdown suppressed cell growth only in the presence of p53, ING2b knockdown had no effect on cell growth, and knockdown of both induced cell cycle arrest and apoptosis independently of p53. ING2a and ING2b have compensatory roles that protect cells from cell cycle arrest and apoptosis and may be involved in development of chemotherapeutic resistance.
Unoki
Motoko
M
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Dr., Bldg. 37, Rm. 3068, Bethesda, MD 20892, USA.
Kumamoto
Kensuke
K
Robles
Ana I
AI
Shen
Jiang Cheng
JC
Zheng
Zhi-Ming
ZM
Harris
Curtis C
CC
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D018398:Homeodomain Proteins; C444654:ING2 protein, human; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins